Posted by: Dan | November 5, 2006

Growth factors and neurite extension

Growth Factor Stimulates Rapid Extension Of Key Motor Neurons In Brain, via ScienceDaily.

This is an exciting study, but I think that in the coming years we will find that cellular signaling through many of the growth factor receptors, also called receptor tyrosine kinases (RTKs), will promote regeneration of neuronal functions in the CNS. In particular, I’m curious about EGF, VEGF, BDNF, and bFGF, and what signaling pathways eminating from their receptors could be utilized in a combination of pharmaceutical enhancement of regenerative therapies. But time will tell.

Anyway, an excerpt from the article below the fold:

A growth factor known to be important for the survival of many types of cells stimulates rapid extension of corticospinal motor neurons — critical brain cells that connect the cerebral cortex with the spinal cord and that die in motor neuron diseases like amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease). In the November 2006 issue of Nature Neuroscience, two investigators from Massachusetts General Hospital (MGH) and the Harvard Stem Cell Institute describe how insulin-like growth factor 1 (IGF-1) dramatically increases the in vitro growth of corticospinal motor neuron (CSMN) axons — projections that carry nerve impulses to the spinal motor neurons that connect to muscles — and that blocking IGF-1 activity reduces that growth in both cultured cells and in living mice.

“Our findings that IGF-1 specifically enhances both the speed and extent of axon outgrowth of corticospinal motor neurons are the first direct evidence of growth factor control over the differentiation of these neurons, ” says Jeffrey Macklis MD, DHST, director of the MGH-Harvard Medical School (HMS) Center for Nervous System Repair, the report’s senior author. “In addition to providing insight into the development and circuit formation of this critical population of neurons, these results might lead to the future ability to treat motor neuron disorders and spinal cord injuries.”

Although their cell bodies are located in the brain, CSMN axons extend down to the neurons they control in the spinal cord — extending as far as three feet in adult humans. These neurons degenerate in ALS and related disorders, and their damage contributes to loss of motor function in spinal cord injuries. Since they are embedded among hundreds of other types of neurons in the cerebral cortex, it has been difficult to study CSMN, and little has been known about cellular and molecular factors that control their growth and development. In order to study growth factor controls over these cells, Macklis and Hande Ozdinler, PhD, a postdoctoral fellow in his laboratory, developed a new way of isolating pure populations of CSMN in culture and found that IGF-1 was a prime candidate for control over CSMN development.


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